False synergy between vancomycin and β-lactams against glycopeptide-intermediate Staphylococcus aureus (GISA) caused by inappropriate testing methods

ABSTRACTThe combination of vancomycin and β-lactams is often considered synergistic and has been recommended for the treatment of glycopeptide-intermediate Staphylococcus aureus (GISA) infections. In this study, the combination of vancomycin or teicoplanin with different β-lactams was tested. When using NaCl 4% w/v, for better expression of heterogeneous resistance to β-lactams, with a longer (48-h) incubation period and a higher (107 CFU/mL) inoculum, the association of vancomycin with β-lactams was antagonistic. However, a synergistic effect was observed for teicoplanin under the same conditions

Total laparoscopic infrarenal aortic aneurysm repair: Preliminary results

ObjectivesWe describe our initial experience of total laparoscopic abdominal aortic aneurysm (AAA) repair.Material and methodsBetween February 2002 and September 2003, we performed 30 total laparoscopic AAA repairs in 27 men and 3 women. Median age was 71.5 years (range, 46-85 years). Median aneurysm size was 51.5 mm (range, 30-79 mm). American Society of Anesthesiologists class of patients was II, III and IV in 10, 19, and 1 cases, respectively. We performed total laparoscopic endoaneurysmorrhaphy and aneurysm exclusion in 27 and 3 patients, respectively. We used the laparoscopic transperitoneal left retrocolic approach in 27 patients. We operated on 2 patients via a tranperitoneal left retrorenal approach and 1 patient via a retroperitoneoscopic approach.ResultsWe implanted tube grafts and bifurcated grafts in 11 and 19 patients, respectively. Two minilaparotomies were performed. In 1 case, exposure via a retroperitoneal approach was difficult and, in another case, distal aorta was extremely calcified. Median operative time was 290 minutes (range, 160-420 minutes). Median aortic clamping time was 78 minutes (range, 35-230 minutes). Median blood loss was 1680 cc (range, 300-6900 cc). In our early experience, 2 patients died of myocardial infarction. Ten major nonlethal postoperative complications were observed in 8 patients: 4 transcient renal insufficiencies, 2 cases of lung atelectasis, 1 bowel obstruction, 1 spleen rupture, 1 external iliac artery dissection, and 1 iliac hematoma. Others patients had an excellent recovery with rapid return to general diet and ambulation. Median hospital stay was 9 days (range, 8-37 days). With a median follow-up of 12 months (range, 0.5-20 months), patients had a complete recovery and all grafts were patent.ConclusionThese preliminary results show that total laparoscopic AAA repair is feasible and worthwhile for patients once the learning curve is overcome. However, prior training and experience in laparoscopic aortic surgery are needed to perform total laparoscopic AAA repair. Despite these encouraging results, a greater experience and further evaluation are required to ensure the real benefit of this technique compared with open AAA repair

Mechanisms of failure to decontaminate the gut with polymixin E, gentamicin and amphotericin B in patients in intensive care.

The objective of the present work was to assess the possible mechanisms of the poor efficiency of selective decontamination of the digestive tract (SDD) in medical and surgical intensive care unit (ICU) patients. Sixty-four consecutive mechanically ventilated patients received gut decontamination with polymixin E, gentamicin and amphotericin B via a nasogastric tube and were assessed for oropharyngeal, gastric and fecal colonization and for the presence of each antibiotic in the stomach and feces. A decrease in fecal colonization with Escherichia coli was observed over 20 days but not with other gram-negative bacteria or gram-positive cocci. Fifteen and 26% of the fecal colonizing gram-negative bacteria were resistant to polymixin E and gentamicin, respectively, at admission. These proportions increased to up to 50% after 16 days of treatment. Although 50% of staphylococci were initially sensitive to gentamicin, all strains were resistant to this drug after four days of SDD. Both antibiotics were found in concentrations of less than 20 micrograms/g in 11 of 38 stools. Of these 38 stools, nine were not contaminated, 20 were colonized with resistant bacteria and 16 with strains sensitive to one antibiotic present in the stool. Therefore, the poor efficiency of gut decontamination observed was probably due to the great proportion of resistant strains on admission of the patients, to the selection of such resistant strains with SDD, to poor intestinal transit of the antibiotics, and to inactivation of the drugs by the feces. These results support stringent monitoring of fecal colonization in patients undergoing SDD in order to detect the fecal carriage of gram-positive and multiresistant gram-negative bacteria

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al

Short-term triple therapy with azithromycin for Helicobacter pylori eradication: Low cost, high compliance, but low efficacy

<p>Abstract</p> <p>Background</p> <p>The Brazilian consensus recommends a short-term treatment course with clarithromycin, amoxicillin and proton-pump inhibitor for the eradication of <it>Helicobacter pylori </it>(<it>H. pylori)</it>. This treatment course has good efficacy, but cannot be afforded by a large part of the population. Azithromycin, amoxicillin and omeprazole are subsidized, for several aims, by the Brazilian federal government. Therefore, a short-term treatment course that uses these drugs is a low-cost one, but its efficacy regarding the bacterium eradication is yet to be demonstrated. The study's purpose was to verify the efficacy of <it>H. pylori </it>eradication in infected patients who presented peptic ulcer disease, using the association of azithromycin, amoxicillin and omeprazole.</p> <p>Methods</p> <p>Sixty patients with peptic ulcer diagnosed by upper digestive endoscopy and <it>H. pylori </it>infection documented by rapid urease test, histological analysis and urea breath test were treated for six days with a combination of azithromycin 500 mg and omeprazole 20 mg, in a single daily dose, associated with amoxicillin 500 mg 3 times a day. The eradication control was carried out 12 weeks after the treatment by means of the same diagnostic tests. The eradication rates were calculated with 95% confidence interval.</p> <p>Results</p> <p>The eradication rate was 38% per intention to treat and 41% per protocol. Few adverse effects were observed and treatment compliance was high.</p> <p>Conclusion</p> <p>Despite its low cost and high compliance, the low eradication rate does not allow the recommendation of the triple therapy with azithromycin as an adequate treatment for <it>H. pylori </it>infection.</p